Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Activation of neuronal caspase-3 by intracellular accumulation of wild-type Alzheimer amyloid precursor protein
Autore:
Uetsuki, T; Takemoto, K; Nishimura, I; Okamoto, M; Niinobe, M; Momoi, T; Miura, M; Yoshikawa, K;
Indirizzi:
Osaka Univ, Inst Prot Res, Div Regulat Macromol Funct, Osaka 5650871, Japan Osaka Univ Osaka Japan 5650871 ulat Macromol Funct, Osaka 5650871, Japan Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Div Dev & Differentiat, Tokyo 1878502, Japan Natl Ctr Neurol & Psychiat Tokyo Japan 1878502 iat, Tokyo 1878502, Japan Osaka Univ, Sch Med, Biomed Res Ctr, Dept Neuroanat, Osaka 5650871, Japan Osaka Univ Osaka Japan 5650871 Ctr, Dept Neuroanat, Osaka 5650871, Japan
Titolo Testata:
JOURNAL OF NEUROSCIENCE
fascicolo: 16, volume: 19, anno: 1999,
pagine: 6955 - 6964
SICI:
0270-6474(19990815)19:16<6955:AONCBI>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROGRAMMED CELL-DEATH; CEREBRAL-ISCHEMIA; DNA FRAGMENTATION; IN-VIVO; NERVOUS-SYSTEM; BETA-PROTEIN; DISEASE; APOPTOSIS; DEGENERATION; ADENOVIRUS;
Keywords:
amyloid precursor protein; caspase-3; apoptosis; adenovirus vector; postmitotic neurons; Alzheimer's disease;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Yoshikawa, K Osaka Univ, Inst Prot Res, Div Regulat Macromol Funct, Yamadaoka 3-2, Osaka 5650871, Japan Osaka Univ Yamadaoka 3-2 Osaka Japan 5650871 5650871, Japan
Citazione:
T. Uetsuki et al., "Activation of neuronal caspase-3 by intracellular accumulation of wild-type Alzheimer amyloid precursor protein", J NEUROSC, 19(16), 1999, pp. 6955-6964

Abstract

Forced overexpression of wild-type Alzheimer amyloid precursor protein (APP) causes postmitotic neurons to degenerate. Caspase-3 (CPP32) is a principal cell death protease involved in neuronal apoptosis during physiological development and under pathological conditions. Here, we investigated whether APP overexpression activates caspase-3 in human postmitotic neurons usingadenovirus-mediated gene transfer. When a recombinant adenovirus vector expressing human wild-type APP695 was infected in vitro into neurally differentiated embryonal carcinoma NT2 cells, only postmitotic neurons underwent severe degeneration. Before neurodegeneration, full-length APP- and A beta-immunoreactive peptides were accumulated in infected neurons, and caspase-3-like protease activity was markedly elevated. Western blot analysis revealed that activated caspase-3 subunits were generated in APP-accumulating neurons. Such neuronal caspase-3 activation was undetectable in NT2 neurons infected with beta-galactosidase-expressing adenovirus. Addition of the caspase-3 inhibitor acetyl-Asp-Glu-Val-Asp-aldehyde to the culture medium significantly reduced the severity of degeneration exhibited by APP-overexpressingneurons. Immunocytochemical analyses revealed that some APP-accumulating neurons contained activated caspase-3 subunits and exhibited the characteristics of apoptosis, such as chromatin condensation and DNA fragmentation. Activation of caspase-3 was also observed in vivo in rat hippocampal neurons infected with the APP-expressing adenovirus. These results suggest that wild-type APP is an intrinsic activator of caspase-3-mediated death machinery in postmitotic neurons.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/12/20 alle ore 16:17:29